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Lysine adducts between methyltetrahydrophthalic anhydride and collagen in guinea pig lung

In English

Författare

  • Bo A Jönsson
  • J S Wishnok
  • P L Skipper
  • W G Stillwell
  • S R Tannenbaum

Summary, in English

The formation of adducts between methyltetrahydrophthalic anhydride (MTHPA), an important industrial chemical and potent allergen, and collagen from guinea pig lung tissue was investigated. Collagen peptides were obtained from the lung tissue by homogenization, defatting, washing, and digestion with collagenase. In experiments in vitro, lung tissue was exposed to 8.4 mumol (50 microCi) of 14C MTHPA. The amount of adducts was 97 nmol MTHPA/g of wet tissue as determined from the bound radioactivity. In a study in vivo, four guinea pigs were injected intratracheally with 8.4 mumol of 14C MTHPA each. The amount of adducts was 0-1.2 nmol MTHPA/g of wet tissue (determined by bound radioactivity). N epsilon-methyltetrahydrophthaloyl-L-lysine (MTHPL) was synthesized and characterized by NMR, UV, and mass spectrometry (MS). A method to analyze MTHPL, after derivatization with methanol and pentafluorobenzoyl chloride, using gas chromatography-MS was developed. Analysis of Pronase-digested MTHPA-exposed lung tissue showed a concentration of 19 nmol MTHPL/g wet lung in vitro and between 0 and 0.15 nmol MTHPL/g wet lung in vivo. Thus, 20% in vitro and 12-15% in vivo of the bound radioactivity was found as adducts with lysine. These results are a first step toward studies of allergenic epitopes in proteins and methods for biological monitoring of exposure to acid anhydrides.

Publiceringsår

1995

Språk

Engelska

Sidor

156-162

Publikation/Tidskrift/Serie

Toxicology and Applied Pharmacology

Volym

135

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Academic Press

Ämne

  • Pharmacology and Toxicology

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1096-0333